Transcriptional factors act directly to activate or inhibit transcription by interacting with DNA sites near specific target genes. A number of factors that directly affect the initiation of transcription of specific genes have been isolated, including receptors for steroid hormones, thyroid hormones or retinoic acid. Other transcription factors bind cis-acting promoter and enhancer elements and may exert actions in a tissue-specific manner. The family of homeobox proteins, originally described as important factors regulating development in Drosophila, is now known to be involved in the development of virtually all animals, many of them are known to be important factors in development while other are involved in the regulation of the expression of certain genes. For example, several of the genes in the HOX-2 family of human homeobox genes are known to be involved in erythropoietin- regulated globin gene expression. In this effort, we plan to develop monoclonal and polyclonal antibodies against four members of the HOX-2 family of genes, and will use them in efforts to define the role these factors play in the control of globin gene transcription.